Study on the ischemia-induced neuronal injuries with special reference to alterations in the intracellular signaling cascades.

在我们的一系列实验中，我们发现N-甲基-D-天冬氨酸(NMDA)受体与细胞内钙信号级联参与了纹状体缺血性损伤及其对靶核的远程影响。此外，脑室内注入GABA受体激动剂可通过移植胎儿纹状体原基来促进纹状体黑质通路在纹状体缺血损伤中的重建。此外，我们建立了纹状体组织的器官型培养技术，然后在体外复制了对纹状体神经元的NMDA神经毒性，这种毒性不被GABA_A受体激活所阻断。此外，纹状体富含蛋白酪氨酸磷酸酶(STEP)的过表达可促进cAMP类似物对PC12细胞的诱导分化，提示STEP可能参与了神经元的建模和/或可塑性。因此，我们有一个计划来阐明一个细胞系是否通过转导STEP基因改变其对缺血/缺氧损伤的易感性。

In a series of our experiments, we have found that N-methyl-D--aspartate (NMDA) receptor coupled with intracellular calcium-signaling cascade is involved in the striatal ischemic injury and its remote effects on the target nuclei. Also, an intraventricular infusion of GABA receptor agonist promotes reformation of the striatonigral pathway by transplant derived from fetal striatal primordia in the striatal ischemic lesion. Furthermore, we have established an organotypic culture technique for the striatal tissue and then reproduced the NMDA-neurotoxicity on the striatal neurons in vitro which was not blocked by an activation of GABA_A receptor. In addition, overexpression of striatal enriched protein tyrosine phosphatase (STEP) was found to promote neuronal differentiation induced by a cAMP analogue in PC12 cells, suggesting that STEP may participate in neuronai modeling and/or plasticity. Therefore, we have a plan to elucidate whether a cell line changes its vulnerability to ischemic/anoxic insult by the STEP gene transfection.